UPDATE: OUTBREAK OF SEVERE ACUTE RESPIRATORY SYNDROME—WORLDWIDE,
2003

MMWR. 2003;52:241-248

3 figures, 1 table omitted

CDC continues to support the World Health Organization (WHO) in the
investigation of a multicountry outbreak of unexplained atypical pneumonia
referred to as severe acute respiratory syndrome (SARS).1 This
report includes summaries of the epidemiologic investigations and public health
responses in several affected locations where CDC is collaborating with international
and national health authorities. This report also describes an unusual cluster
of cases associated with a hotel in Hong Kong and identifies the potential
etiologic agent of SARS. Epidemiologic and laboratory investigations of SARS
are ongoing.

As of March 26, a total of 1,323 suspected and/or probable SARS cases
have been reported to WHO from 14 locations,2 using the WHO case
definition or country-specific variations.*3 These reported SARS
cases include 49 deaths (case-fatality proportion: 4%). The Chinese authorities
have reported 792 suspected/probable cases, including 31 deaths, which occurred
in Guangdong province during November 16, 2002–February 28, 2003.

CDC is assisting in epidemiologic investigations of cases in Hong Kong,
Vietnam, Taiwan, and Thailand. CDC also is conducting surveillance and prevention
activities in the United States.

Hong Kong. As of March 25, the Hong Kong Department
of Health (DH) reported 290 suspected and probable SARS cases. Beginning on
March 11, an increase in acute pneumonia cases among health-care workers (HCWs)
at hospital 1 in Hong Kong was reported to DH. Epidemiologic investigation
has linked these cases to an index patient (Patient J) who visited a friend
in hotel M in late February, became ill a few days later, and was admitted
to hospital 1 on March 4. Patient J visited hotel M while patient A, an ill
visitor from Guangdong province, was staying there.

As of March 25, a cluster of 13 persons with suspected/probable SARS
are known to have stayed at hotel M. The index patient (patient A) had onset
of symptoms on February 15. He traveled from Guangdong province to Hong Kong
to visit family and stayed on the ninth floor of the hotel on February 21.
He was admitted to hospital 2 on February 22 and died the next day. Four HCWs
and two of his family members subsequently became ill; one family member died.
Of the 12 other patients linked to hotel M, 10 were in the hotel the same
day as the index patient; the other two patients (patients L and M) stayed
in the hotel during the time that three other symptomatic patients were guests
in the hotel. Nine of the 13 patients, including patient A, stayed on the
ninth floor; one stayed on the 14th floor; one stayed on the 11th floor; and
two stayed on both the ninth and 14th floors. Epidemiologic investigations
have identified patients from this cluster as index patients in subsequent
clusters in Hong Kong and other areas. Patient B is the index patient for
the outbreak in Hanoi involving 59 HCWs and close contacts and also is linked
to one case in Thailand. Patients C, D, and E are associated with 70 cases
in Singapore and three cases in Germany. Patient F is linked with a cluster
of 16 other cases in Toronto.4 Patients H and J are linked with
outbreaks among HCWs in other hospitals in Hong Kong. Patient L appears to
have become infected during his stay at hotel M, with subsequent transmission
to his wife, patient M.

As of March 25, six hospitals and one clinic in Hong Kong have reported
nosocomial transmission to HCWs following admission of persons with SARS.
The suspected index patients of three of the seven nosocomial clusters reported
in Hong Kong have been associated with hotel M.

Hong Kong health authorities have implemented enhanced infection-control
procedures in all hospitals in Hong Kong, including more stringent barrier
and respiratory protection for HCWs, at least daily environmental disinfection
of affected wards, and cohorting of SARS patients. New cases among HCWs have
declined following implementation of these new guidelines. However, new cases
continue to be reported, predominantly among close contacts† of known
patients.

Vietnam. As of March 24, the Vietnamese Ministry
of Health in Hanoi has reported 59 probable SARS cases. The probable index
patient (patient B) was an Asian-American businessman aged 47 years who had
visited Hong Kong before traveling to Hanoi. During his visit to Hong Kong,
he had stayed at hotel M on the same floor, and during the same time, as patient
A. Patient B became ill after arrival in Hanoi on February 23 and was hospitalized
with lower respiratory symptoms on February 26. On March 2, he was placed
on mechanical ventilation. On March 5, he was medically evacuated to a hospital
in Hong Kong and died on March 12. By March 5, secondary probable SARS cases
were identified among HCWs in Hanoi. All probable SARS cases reported as of
March 24 in Hanoi have been linked through primary or secondary exposure to
the same hospital. Two patients who were exposed to hospitalized SARS patients
traveled subsequently to Thailand and France and are not included in these
numbers.

The government of Vietnam has implemented control activities in Hanoi
and throughout the country, including daily follow-up of contacts of probable
SARS cases and community surveillance for suspected SARS cases. Infection-control
practices to prevent nosocomial transmission have been implemented at Hanoi
hospitals with probable SARS cases. Nosocomial cases have decreased since
the initial peak of cases linked to exposure to the index patient.

Thailand. As of March 23, the Ministry of Public
Health in Thailand has reported four suspected/probable cases. Dates of illness
onset ranged from March 11 to March 18. Of these four ill persons, three reported
travel to Hong Kong during the week before illness onset; the other person
is a physician who cared for SARS patients in Hanoi. Thailand has begun to
implement hospital infection control procedures on the presumption of airborne
spread. Gowns, gloves, and N-95 masks are widely available in Thailand. As
of March 26, surveillance has not documented spread of infection to HCWs.
However, one HCW from Thailand became infected while investigating the outbreak
in Hanoi.

Taiwan. As of March 25, the Taiwan Department
of Health has reported six probable cases. Dates of illness onset ranged from
February 25 to March 17. Of these six ill persons, four reported travel to
Guangdong province and Hong Kong during the week before illness onset; none
of them had stayed at hotel M. The other two cases occurred in family members
of the first patient. Two patients required mechanical ventilation but have
improved clinically.

On the basis of presumed airborne spread of SARS, Taiwan has aggressively
implemented and monitored strict infection-control procedures. Negative pressure
rooms and N-95 respirators are uniformly available for hospitalized patients.
Active surveillance has not identified nosocomial transmission. Epidemiologic
studies are under way to determine specific risk factors for transmission.

United States. As of March 26, CDC has received
51 reports of suspected SARS cases from 21 states, identified using the CDC
updated interim case definition (see sidebar). The first suspected case was
identified on March 15, in a man aged 53 years who traveled to Singapore and
became ill on March 10. Four clusters of suspected cases have been identified,
three of which involved a traveler who had visited Southeast Asia (including
Guangdong province, Hong Kong, or Vietnam) and a single family contact. One
of these clusters involved suspected cases in patients L and M, who had stayed
together at hotel M during March 1-6, when other hotel guests were symptomatic.
Patient L became sick on March 13 after returning to the United States. His
wife, patient M, became ill several days after the onset of her husband's
symptoms, suggesting secondary transmission. Three patients in the United
States with suspected SARS (patients I, L, and M) reported staying at hotel
M when other persons staying in the hotel were symptomatic. The fourth cluster
began with a suspected case in a person who traveled in Guangdong province
and Hong Kong. Two HCWs subsequently became ill at the U.S. hospital where
this patient was admitted.

Laboratory investigations. On March 24, CDC
announced that laboratory analysis had identified a previously unrecognized
coronavirus in patients with suspected or probable SARS. The new coronavirus
was isolated in Vero E6 cells from clinical specimens of two patients in Thailand
and Hong Kong with suspected SARS. The isolate was identified initially as
a coronavirus by electron microscopy (EM). The identity was corroborated by
results of immunostaining, indirect immunofluorescence antibody (IFA) assays,
and reverse transcriptase-polymerase chain reaction (RT-PCR) with sequencing
of a segment of the polymerase gene. IFA testing of sera and RT-PCR analysis
of clinical specimens from six other SARS cases were positive for the new
coronavirus. Coronavirus particles also were identified by EM in cells obtained
by bronchial lavage from a patient with SARS. Sequence analysis suggests that
this new agent is distinct from other known coronaviruses. Other laboratories
collaborating in the WHO-led investigation have found similar results and
also have isolated a different virus, human metapneumovirus, from some patients
with suspected SARS. Information is insufficient to determine what roles these
two viruses might play in the etiology of SARS.

CDC Editorial Note:

Cases of SARS continue to be reported from around the world. These cases
are linked primarily to areas with ongoing transmission, with some reports
of secondary local transmission. Transmission has been reported in Guangdong
Province, Hong Kong, Singapore, and Hanoi. In Canada, transmission appears
to be limited to a well-defined population of HCWs and close contacts. In
Taiwan, limited transmission has occurred to family members but not to HCWs.
Chinese authorities have updated the number of cases in Guangdong province
and confirmed ongoing disease activity. The numbers of reported cases in Canada,
Singapore, and the United States also continue to increase.2 Transmission
in hospitals and households continues to occur. In addition, reports have
been received of possible transmission on ships and planes and in offices.
On the basis of available information, country-specific efforts to limit and
halt transmission have included enhancing surveillance, improving infection-control
measures in hospitals and homes, selectively closing hospitals and schools,
furloughing hospital staff, issuing travel advisories, restricting movement
of patients with suspected SARS, and establishing quarantines of exposed persons.
In the United States, CDC has issued travel advisories and developed infection-control
guidelines; efforts have been focused on rapid identification and early isolation
of symptomatic persons whose illnesses meet the CDC case definition.

The summary of the demographic, clinical, and transmission patterns
from the reported areas documents some disparities in case-fatality proportion
with pneumonia, and ease of transmission. The data also highlight gaps in
knowledge about the epidemiology of this new syndrome. Some differences probably
reflect concomitant differences in case definition and surveillance methodologies.
However, because of the nonspecific case definition, all reported cases might
not represent a single clinical entity. Confirmation of the etiology and development
of a diagnostic test should help to resolve these discrepancies.

Although the mechanism of SARS transmission remains unclear, on the
basis of the reported exposures for the majority of cases (i.e., household
contacts and HCWs), droplet and contact transmission appear to be the predominant
modes. The cases in the hotel M cluster and certain hospital clusters involving
seriously ill patients suggest airborne or fomite transmission. Therefore,
infection-control recommendations should include precautions to prevent airborne,
droplet, and contact transmission. With the introduction of these control
measures, decreases in the reported incidence of SARS have been reported in
Hong Kong.

Although the etiologic agent has not been confirmed, laboratory data
indicate that a metapneumovirus or a coronavirus are possible agents. Infection
with a metapneumovirus, (i.e., enveloped, single-stranded RNA virus) has been
associated previously with respiratory disease with much less frequent occurrence
of severe disease than SARS. Coronaviruses are enveloped, single-stranded
RNA viruses that infect both humans and animals.5 The known human
coronaviruses can cause serious infections of the lower respiratory tract
in children and adults and necrotizing enterocolitis in newborns.5,6 Coronaviruses are able to survive on environmental surfaces for up
to 3 hours.6 Coronaviruses might be transmitted person-to-person
by droplets, hand contamination, fomites, and small particle aerosols.7

Clinicians evaluating suspected cases should use standard precautions
(e.g., hand hygiene) together with airborne (e.g., N-95 respirator) and contact
(e.g., gowns and gloves) precautions.8 Until the mode of transmission
has been defined more precisely, eye protection also should be worn for all
patient contact. As more clinical and epidemiologic information becomes available,
interim recommendations will be updated.

The international spread of disease underscores the need for strong
global public health systems, robust health service infrastructures, and expertise
that can be mobilized quickly across national boundaries to mirror disease
movements. The Institute of Medicine has recently issued recommendations for
invigorating the response to emerging infectious diseases that reflect these
needs, including the development of a comprehensive system of surveillance
for global infectious diseases, the enhancement of disease reporting, the
development of diagnostic tests, and the formulation and distribution of guidelines
on diagnosis.9

Respiratory illness of unknown etiology with onset since February 1,
2003, and the following criteria:

Measured temperature >100.4°F (>38.0°C)

One or more clinical findings of respiratory illness (e.g., cough,
shortness of breath, difficulty breathing, hypoxia, or radiographic findings
of either pneumonia or acute respiratory distress syndrome)

Travel within 10 days of onset of symptoms to an area with suspected
or documented community transmission of SARS,‡ (excluding areas with
secondary cases limited to health-care workers or direct household contacts)
OR

Close contact§ within 10 days of onset of symptoms with either
a person with a respiratory illness and travel to a SARS area or a person
under investigation or suspected of having SARS

*As of March 22, 2003.

†Suspected cases with either radiographic evidence of pneumonia
or respiratory distress syndrome, or evidence of unexplained respiratory distress
syndrome by autopsy, are designated "probable" cases by the World Health Organization
case definition.

§Close contact is defined as having cared for, having lived with,
or having had direct contact with respiratory secretions and/or body fluids
of a patient suspected of having SARS.

References: 9 available

*WHO defines3 a suspected case as an illness that occurs
in a person presenting after February 1, 2003, with a history of high fever
(>100.4°F [ >38°C]); one or more respiratory symptoms, including cough,
shortness of breath, and difficulty breathing; and close contact within 10
days of symptoms onset with a person in whom SARS has been diagnosed and/or
a history of travel within 10 days of onset of symptoms to an area with reported
foci of SARS transmission. WHO defines a probable case as a suspected case
of illness that occurs in a person with either (1) chest radiograph findings
of pneumonia or respiratory distress syndrome (RDS) or (2) unexplained respiratory
illness resulting in death, with autopsy examination demonstrating pathology
of RDS but no identifiable cause.

†Persons who have cared for, lived with, or had direct contact
with respiratory secretions and body fluids of a person with SARS.

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